The present invention provides novel compositions of matter and processes for their preparation. Particularly, the present invention relates to novel chemical intermediates and associated processes for the preparation of furochromones. Most especially, the present invention provides for the preparation of novel antiatherosclerotic furochromones, particularly khellin analogs.
Khellin and related compounds are known to exert a wide variety of pharmacological effects. Recently, khellin has been reported to exhibit useful antiatherosclerotic activities. Moreover, numerous analogs of khellin likewise are known to exert useful antiatherosclerotic effects. For example, 7-methylthiomethyl-4,9-dimethoxyfurochromone is described in U.S. Pat. No. 4,284,569 as such a useful antiatherosclerotic substance.
Methods for the total synthesis of khellin are known. For example, pyrogallol has been employed as a starting material for the synthesis of furochromones such as khellin. See Clarke, J. R., et al., J. Chem. Soc., 302 (1949), Baxter, R. A., et al., J. Chem. Soc., S30 (1949), Schonberg, A., et al., J. Am. Chem. Soc., 73: 2960 (1951), Murti, V. V. S., et al., Proc. of the Indian Acad. of Sci., 30A: 107 (1949), and Geissman, T. A., et al., J. Am. Chem. Soc., 73: 1280 (1951). Also descriptive of the synthesis of khellin are Spath, E., et al., Chem. Ber., 71: 106 (1938), Dann, O., et al., Chem. Ber., 83: 2829 (1960), Dann, O., et al., Ann. Chem., 605: 146 (1957), and Murti, V. V. S., et al., J. Sci. Ind. Res. (India), 8B: 112 (1949). See also U.S. Pat. No. 2,680,119 describing the synthesis of khellin and related compounds.
Other references describing the synthesis of intermediates useful in the preparation of khellin for analogs include: Aneja, R., et al., Chem. Ber., 93: 297 (1960), Aneja, R., et al., J. Sci. Ind. Res. (India), 17B: 382 (1958), Gardner, T. S., et al., J. Org. Chem., 15: 841 (1950), and Rowe, L. R., et al., Indian J. Chem., 5: 105 (1967).
Accordingly, the references cited above describe the preparation of 1-(6-hydroxy-4,7-dimethoxy-5-benzofuranyl)-ethanone. Also known is the related compound 6-hydroxy-4,7-dimethoxy-5-benzofurancarboxylic acid, methyl ester, described by Musante, C., Gazz. Chim. Ital., 88: 910 (1958).